Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases, ERKs. This kinase cascade governs the proliferation and differentiation of different cell types (Ferrel Jr. Curr. Top. Dev. Biol. 33:1-60, 1996; Morrison and Cutler, Curr. Opin. Cell Biol. 9:174-179, 1997).
In metazoans the Ras/Raf-1/MEK/ERK module is a ubiquitously expressed signaling pathway that conveys mitogenic and differentiation signals from the cell membrane to the nucleus (Ferrel Jr. Curr. Top. Dev. Biol. 33:1-60, 1996). This kinase cascade appears to be spatially organized in a signaling complex nucleated by Ras proteins (Moodie et al. Science 260:1658-1661, 1993). The regulation of the Ras/Raf-1/MEK/ERK module is complex and may include associations with scaffolding and regulatory proteins (Schaeffer et al. Science 281:1668-1671, 1998).